We will undertake the synthesis and evaluation in several selected enzyme systems of a series of pteridines, azapteridines, and related heterocyclic systems of potential pharmacological and biochemical utility. Included in the enzymatic studies will be a number of dihydrofolate reductase systems, mammalian liver aldehyde oxidases, rat liver phenylalanine hydroxylase, bovine adrenal tyrosine hydroxylase, bovine tryptophan hydroxylase, xanthine oxidase, aldehyde oxidase, and adenosine deaminase. Our target compounds for synthesis, designed on the basis of the pharmacological studies carried out thus far in the program, include 2,4-diaminopteridines and 7-azapteridines with multifunctional C-6 substituents (as biopterin and neopterin analogs), a series of 2,4-diamino-6-(cycloalkylmethyl)pteridines, and a number of 6-acylpteridines designed primarily as intermediates for other 6-substituted pteridines. Our studies on the development and exploitation of new synthetic methodologies in heterocyclic chemistry will be continued. Our goal is the discovery of useful compounds for the treatment of neoplastic disease, certain hypertensive states, Parkinson's disease, and a variety of protozoal diseases, and for studies of drug metabolism. BIBLIOGRAPHIC REFERENCES: E.C. Taylor and F. Sowinski, The Reaction of 6-Amino- and 6-Hydrazinopyrimidines with Diethyl Azodicarboxylate. A New Method for Carbon-5 Functionalization of Pyrimidines, J. Org. Chem., 39, 907 (1974). J.J. McCormack, Xanthine Oxidase and Adenosine Deaminase in Commercial Bovine Spleen Phosphodiesterase Preparations, Biochem. Biophys. Res. Commun., 63, 1161 (1975).